tbuckley/cabot-search huggingface dataset:
Evaluating Ethnic Variations in the Risk of Infections in People With Prediabetes and Type 2 Diabetes: A Matched Cohort Study
Authors: Iain M. Carey, Julia A. Critchley, Umar A.R. Chaudhry, Stephen DeWilde, Elizabeth S. Limb, Derek G. Cook, Peter H. Whincup, Tess Harris
Journal: Diabetes Care (2023)

People living with type 2 diabetes (T2D) are at higher infection risk, but it is unknown how this risk varies by ethnicity or whether the risk is similarly observed in people with nondiabetic hyperglycemia ("prediabetes").
Case 11-2023: A 67-Year-Old Man with Mantle-Cell Lymphoma and Hypoxemia
Authors: Eric P. Schmidt, Jo-Anne O. Shepard, Li Liu
Journal: New England Journal of Medicine (2023)

A 67-year-old man with mantle-cell lymphoma was admitted for hypoxemia that did not abate with supplemental oxygen. CT pulmonary angiography showed pulmonary emboli. A diagnostic test was performed.
Extracellular vesicles: Expanding the landscape for next-generation delivery strategies in gene and cell therapy
Authors: Robert Frederickson, Thomas Ritter, Kevin V. Morris
Journal: Molecular Therapy (2023)

The last two decades have been busy for the field of gene and cell therapy, culminating in a growing number of approved products representing diverse therapeutic platforms, with many others in various stages of translational and clinical development. These products nevertheless have their origins in basic research in gene transfer and recombinant DNA technology pursued in the last quarter of the last century. Basic research in gene and cell therapy continues to be a strong driver of innovation and problem solving. RNA interference and gene-editing platforms such as CRISPR-Cas are two relevant recent examples that have found their way rapidly into the clinic. However, those who have worked in these fields for a long time know that the main hurdle to success has always been delivery. A therapeutic platform might work well in cultured cells or small animal models, only to fail when tested in humans or large animal models, either owing to immune system interference or the failure of sufficient active product to reach its target cell or tissue. Most gene and cell therapy products to date involve the use of viral-based vectors, but there is much ongoing work to develop nonviral alternatives that can mimic the delivery capacity of viral vectors. In the past decade, increased attention has been paid to the potential and biology of extracellular vesicles or EVs as potential delivery agents.
Insights into the metastatic cascade through research autopsies
Authors: Sonya Hessey, Petros Fessas, Simone Zaccaria, Mariam Jamal-Hanjani, Charles Swanton
Journal: Trends in cancer (2023)

Metastasis is a complex process and the leading cause of cancer-related death globally. Recent studies have demonstrated that genomic sequencing data from paired primary and metastatic tumours can be used to trace the evolutionary origins of cells responsible for metastasis. This approach has yielded new insights into the genomic alterations that engender metastatic potential, and the mechanisms by which cancer spreads. Given that the reliability of these approaches is contingent upon how representative the samples are of primary and metastatic tumour heterogeneity, we review insights from studies that have reconstructed the evolution of metastasis within the context of their cohorts and designs. We discuss the role of research autopsies in achieving the comprehensive sampling necessary to advance the current understanding of metastasis.
5613260 A PHASE -- IIA-IIB, OPEN LABEL, SINGLE CENTER TRIAL TO STUDY SAFETY, TOLERABILITY AND EFFICACY OF MEMANTINE AS SUPPORTIVE LONG-TERM TREATMENT OF SICKLE CELL PATIENTS: TRIAL DESIGN AND ENROLLMENT
Authors: C.L. Levin, A.K. Koren, S.S.P. Peretz, L.L. Livshits, A.M. Makhro, A.B. Bogdanova, M.G. Gassmann
Journal: HemaSphere (2023)

Background: Sickle cell disease (SCD) is a life-threatening hematological disorder with a high rate of long-term comorbidities and a significant socioeconomic burden. Anemia, vaso-occlusive and pain crises, infections, and a high rate of long-term comorbidities are hallmarks of SCD. The pathophysiology of SCD is due to a single point mutation (Glu6Val) that causes polymerization of the mutant hemoglobin (HbS), resulting in red blood cells (RBC) sickling. Inflammation, hemolysis, microvascular obstruction, and organ damage characterize the clinical expression of SCD. The standard of care includes Hydroxycarbamide, symptomatic treatment, blood transfusions, new drugs, and bone marrow transplant as curative therapy. Our recent findings showed that N-methyl D-aspartate receptors (NMDARs) are up-regulated SCD-RBCs and Ca2+ uptake via NMDARs affects SCD-RBC hydration, and hypoxia-induced sickling (Hanggi P. et al., 2014). Inhibition of NMDARs with Memantine, a drug used in Alzheimer’s disease, emerges as a novel treatment in SCD. Memantine administration in 6 SCD adults demonstrated safety (Hegemann I. et al., 2020); and suggested a reduction of RBCs irreversible sickling (Makhro A, et al., 2020). Aims: This phase IIa-IIb open-label, single-center trial aims to study the safety, tolerability, and efficacy of Memantine in adults and teenagers with SCD (NCT03247218). Methods: This trial enrolled 23 SCD (SS and Sβ Thalassemia) 17 patients received Memantine for at least one year period, Hydroxycarbamide was continued administered. Starting dose of Memantine was 5 mg/day with escalation every 3 months, up to 15 mg/day in teenagers and up to 20 mg/day for adults. Patients were followed up monthly, a total of 6762 patients/days of follow-up were summarized. Results: The only safety events reported were transient headache and constipation in two patients; no adverse side effects were noticed. Overall, the number of admission days and emergency room visits decreased compared to the pre-screen period. The hemoglobin and fetal hemoglobin levels remain stable despite less use of blood transfusions; based on preliminary laboratory analysis a trend of reduction in hemolytic and inflammatory parameters can be noticed. Conclusions: The results of this phase IIa-IIb trial suggested safety and probable clinical benefit in long-term treatment with Memantine in SCD adolescents and adults. Full results of this trial are anticipated at the end of 2022 and a phase III trial will be required for the final assessment of the clinical benefit of Memantine treatment in SCD. References 1. Hanggi P. et al., Br J Haematol. 2014;167:252–264 2. Hegemann I, et al., Hemasphere. 2020;4(4):e452 3. Makhro A, et al., eJHaem. 2020;190:1–12).
5613312 PLASMATIC MICROPARTICLES AS POTENTIAL BIOMARKERS IN THE PREVENTIVE DIAGNOSIS OF BETA THALASSEMIA
Authors: M. Chebbi, K. Khalfaoui, S. Saidani, I. Safra, M. Barmate, D. Chaouechi, M. Ben Khaled, M. Ouederni, F. Mellouli, S. Menif, I. Moumni
Journal: HemaSphere (2023)

Background: Plasmatic microparticles (MPs) are submicron (0.1–1 μm) extracellular vesicles that shed during plasma membrane remodeling in response to cell activation and apoptosis. Over the years, microparticles have evolved from their initial status being a cellular discharge mechanism, by which the cell got rid of unwanted materials, they are now considered as functional units produced in a regulated manner and having an important role in the maintenance of homeostasis. However, MPs also participate in the pathophysiology of several diseases such as beta thalassemia. It is a hemoglobinopathy characterized by reduced or absent synthesis of the beta-globin chain resulting in the excessive accumulation of unpaired alpha-globin chains which causes structural and functional alterations of the cytoplasmic membrane of thalassemic red blood cells. These alterations induce membrane budding and the release of MPs, which increases the risk of thrombotic complications observed in beta thalassemia patients. Aims: Therefore, our study suggests the research for plasmatic microparticles as potential cellular biomarkers and the establishment of a new innovative and predictive diagnosis strategy in order to avoid the thrombotic complications of beta thalassemia. Methods: Blood samples were taken from polytransfused beta thalassemia major patients clinically diagnosed at the National Bone Marrow Transplant Center in Tunis and from healthy donors. A cellular study was carried out by flow cytometry in order to quantify the apoptotic MPs derived from erythrocytes, platelets and endothelial cells using different antibodies and specific fluorescent dyes. Results: Our results showed a statistically significant increase in the number of apoptotic MPs, which suggests a high rate of apoptosis in the cells of the patients compared to those of the healthy controls. We also found that MPs derived from erythrocytes and endothelial cells were clearly elevated in beta thalassemia patients, suggesting their potential contribution to thrombotic risk. Conclusion: This discovery makes it possible to consider MPs as potential cellular biomarkers for preventive diagnosis in beta thalassemia. References 1. Romana et al. Microparticles in sickle cell disease. Clinical Hemorheology and Microcirculation 2018; 68(2-3), 319-329. 2. Taher et al. β-Thalassemias. The New England Journal of Medicine 2021; 384 (8): 727-43. 3. Lugo-Gavidia et al. Role of Microparticles in Cardiovascular Disease: Implications for Endothelial Dysfunction, Thrombosis, and Inflammation. Hypertension 2021; 77 (6): 1825-44.
5610603 CLINICAL AND GENETIC PREDICTORS OF SICKLE CELL NEPHROPATHY IN MALAWI
Authors: K.H.B. Banda, J.M. Morrice, G.C. Chagaluka, V.N. Nembaware, A.W. Wonkam
Journal: HemaSphere (2023)

Background: Sickle Cell Nephropathy (SCN) affects 5-18% of Sickle Cell Disease (SCD) patients and accounts for a large proportion of both morbidity and mortality. Certain clinical and genetic factors have been shown to either delay or promote the progression of SCN. Despite an overwhelming majority of those affected by SCD residing on the African continent, very little research has been done on these populations. Aims: This study proposes to investigate both clinical and genetic factors that may be used to identify those at risk of developing chronic renal failure in a Malawian cohort. This conference presentation proposes to compare our initial results to those of other countries. Methods: Participants are currently being recruited, in a cross-sectional study, from weekly Sickle Cell Clinics at Kamuzu Central Hospital in Lilongwe, Malawi. Blood and urine samples are being collected. Results: Preliminary data shows that 17.9% of patients have microalbuminuria. After performing genetic tests, we expect to find an association between SCN and known genetic variants and potentially identify novel variants. Summary/Conclusion: The information garnered from this study will potentially allow for earlier medical intervention and a lowered morbidity and mortality. Furthermore, this research may serve as a launch pad for future studies in SCD in both Malawi and the region and could facilitate the development of treatment protocols for those affected. References 1. Platt et al, New England Journal of Medicine 1994; 23:1639 2. Geard et al, Br J Haematol. 2017; 4: 629 3. McClellan et al, Br J Haematol. 2012; 159: 360
Long Noncoding RNA Signatures as Cancer Biomarkers
Authors: Aina M. Mas, Maite Huarte
Journal: Journal of Clinical Oncology (2023)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Long Noncoding RNA Expression Independently Predicts Outcome in Pediatric Acute Myeloid Leukemia. February 16, 2023 ARTICLE CITATION DOI: 10.1200/JCO.23.00381 Journal of Clinical Oncology - published online before print April 12, 2023 PMID: 37043713 Long Noncoding RNA Signatures as Cancer Biomarkers Aina M. Mas , PhD1,2xAina M. MasSearch for articles by this author and Maite Huarte , PhD1,2xMaite HuarteSearch for articles by this author Show More 1Center for Applied Medical Research, University of Navarra, Pamplona, Spain2Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain https://doi.org/10.1200/JCO.23.00381 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologySUPPORTSupported by PID2020-113683GB-100/funded by MCIN/AEI/10.13039/501100011033, La Caixa Foundation (LCF/PR/HR21/00176), European Research Council Consolidator 771425, and Worldwide Cancer Research 20-0204 grants (M.H.); and Ministerio de Economía y Competitividad REF: BES2015-074569 cofounded by FSE (A.M.M.).AUTHOR CONTRIBUTIONSConception and design: All authorsManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTLong Noncoding RNA Signatures as Cancer BiomarkersThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).No potential conflicts of interest were reported. Companion Long Noncoding RNA Expression Independently Predicts Outcome in Pediatric Acute Myeloid Leukemia
5613458 BLOOD MICROPARTICLES: A TOOL OF EVALUATING THE EFFECT OF TRANSFUSION IN SICKLE CELL DISEASE PATIENTS
Authors: K. Khalfaoui, M. Chebbi, I. Safra, M. Barmate, D. Chaouechi, M. Benkhaled, M. Ouederni, F. Mellouli, S. Menif, I. Moumni
Journal: HemaSphere (2023)

Background: Blood microparticles (MPs) are phospholipid microvesicles derived from cell membranes. Typically, they range in size from 0.1 μm to 1.0 μm and they are released upon oxidative stress, cell activation, injury or apoptosis. MPs have acquired a biological and clinical interest and are recognized as entities able to modulate many biological functions. Literature suggests that they may have a role in the pathophysiology and downstream manifestations of sickle cell disease (SCD). Aims: This present study was carried out to determine MPs profiles in patients with SCD before and after transfusion and to compare these profiles with healthy subjects. Materials: Twenty healthy donors and twelve polytransfused patients with SCD recruited from National Bone Marrow Transplant Center were recruited in this study. None of the patients was transfused for at least 3 weeks before sampling. The blood samples obtained were analyzed for circulating MPs by flow cytometry. The cellular origin was determined by a multiple labeling with specific antibodies and dyes. Results: A high level of apoptotic, platelets, and endothelial MPs with the predominance of the number of erythrocyte MPs was detected in SCD patients compared to healthy donors. This suggests that erythrocytes MPs may contribute to thrombotic risk in sickle cell patients. Moreover, after transfusion most subjects register a decreased number of different types of MPs. Conclusion: Transfusion is an effective treatment option in patients with SCD, as it seems that it decreases the abnormally elevated levels of MPs. References 1. Hebbel et al, Br J Haematol. 2016;174(1):16-29. 2. Kasar et al, Thromb Thrombolysis. 2014;38(2):167-175. 3. Nader et al, Front Immunol. 2020;11:551441. 4. Romana et al, Clin Hemorheol Microcirc. 2018;68(2-3):319-329.
5612535 THE IMPACT OF COVID19 PANDEMIC ON TRANSFUSION DEPENDENT -THALASSEMIA MANAGEMENT: EXPERIENCE OF A SINGLE PEDIATRIC TREATMENT CENTER
Authors: M.V. Maria Vousvouki, A.T. Aikaterini Teli, A.A. Alkistis Adramerina, L.T. Labib Tarazi, M.E. Marina Economou
Journal: HemaSphere (2023)

Background: Health care systems have been facing COVID19 pandemic around the world for almost two years. Transfusion dependent (TDT) β-thalassemia patients represent a vulnerable group,totally dependent upon hospital-based services. Aims: Aim of the present study was to evaluate the impact of COVID19 pandemic on management of TDT patients in a single pediatric treatment center in Northern Greece. Methods: Patient records were reviewed in order to assess changes in management before and during the 24-month pandemic in Greece (03/01/2018-29/02/2020 and 03/01/2020 -28/02/2022, respectively) in terms of transfusion volume and transfusion frequency, mean value of pretransfusional hemoglobin, as well as laboratory parameters reflecting iron overload (ferritin levels, liver and heart MRI). Results: The study included 28 patients, 19 male (67.8%) and 9 female (32.2%), with an age range of 8 to 21 years. Mean number of hospital visits for transfusion was 19.97 ± 3,52/ year prior to the pandemic and 22.38 ± 4.35/year during the pandemic (p: 0.003). Average transfusion volume was 176.18ml ± 38.32/kg/year και 178.67 ± 37.64ml/kg/year, respectively (p: 0.54). With regards to hemoglobin level, mean value was 9.56 ± 0.42g/dl prior to the pandemic and 9.45 ± 0.48gr/dl during the pandemic period. As to iron overload, mean ferritin level was 1362.05 ± 517.56 ng/mL prior to the pandemic and 1021.27 ± 508.92 ng/mL during the latter time period (p:0.016). Out of 28 enrolled patients, 26 underwent heart and liver MRI before pandemic and 23 during the pandemic period. Mean LIC values were 6.84 ± 7.37 mg/gdw and 6.43 ± 6.46 mg/gdw (p: 0.97) before and during the pandemic, respectively (p:0.97). Myocardial MRI values were within normal limits both before and during the pandemic. Summary-Conclusion: Covid19 pandemic did not seem to negatively affect the primary goal of transfusion therapy (pretransfusion Hb), even if an increased number of visits was required in order to transfuse the same blood volume - due to limited availability of blood units per visit. Of interest, pandemic conditions appeared to favor patient adherence to chelation therapy. Reference 1. Jean-Mignard E et al, Transfusion Clinique et Biologique 2022; 29: 70-74
5597349 VITAMIN C AND VITAMIN K2 AS RISK FACTORS FOR OSTEOPOROSIS IN CHILDREN WITH B- THALASSEMIA
Authors: l.M.S. Sherief, A.S.A. Ahmed, A.M.B. Baraka, M.M.Z. Zakaria, M.R.Q. Rquwaydir
Journal: HemaSphere (2023)

Background: Osteoporosis and related fractures have emerged as an important cause of morbidity in patients with B-thalassemia. Many risk factors are attributed to development of Osteopenia and osteoporosis among those patients. Moreover a few studies reported the relation between the osteoporosis and vitamin C and vitamin K2. Aim: The aim of this study was to investigate the relation between the levels of vitamin C and vitamin K2 and risk of development of osteoporosis in children and adult with Beta-Thalassemia major. Methods: This cross-sectional study was carried on 66 β-thalassemia patients and thirty-three age and sex matched control. Their mean age was 15.78±3.9 years. Complete physical examination was performed for all patients in addition to assessing anthropometric measurements. All patients were subjected to routine laboratory investigations, in addition to Vitamin K2, Vitamin C and 25-OH- cholecalciferol assay using ELISA were performed. Bone Mineral Density (BMD) was measured by the Dual Energy X-ray Absorption (DEXA) scan method. Results: the mean vitamin K2 level was significantly lower in patients compared to controls (146.08 ± 85.5 ng/l and 277.78 ± 194.6 ng/l respectively. also, the mean vitamin C level was significantly lower in patients compared to controls (86.27 ± 55.34ng/l and 102.98 ± 75.93 ng/l respectively. Osteopenia and osteoporosis were present in 30.3% and 36.4% of patients respectively compared to 0% in controls where the mean BMD in lumber spine (L1-L4) and femoral neck on both sides was significantly lower in patients compared to controls. There was significant positive correlation between vitamin k2 level and each of body mass index, BMD of (lumber spine, left femur and total hips). Conclusion: Bone mineral density was significantly impaired in patients with b- thalassemia major. Patients with reduced levels of vitamin K2 and vitamin C are at higher risk of developing osteopenia and or osteoporosis. Reference 1. Finck etal,Nutr Res REV 2014;27(2):268.
Working, Low Income, and Cancer Caregiving: Financial and Mental Health Impacts
Authors: Cathy J. Bradley, Sara Kitchen, Kelsey M. Owsley
Journal: Journal of Clinical Oncology (2023)

Approximately 6 million people provide caregiving to people diagnosed with cancer. Many must remain employed to support their household and to have access to health insurance. It is unknown if caregiving for a spouse diagnosed with cancer is associated with greater financial and mental stress relative to providing care for a spouse with different conditions.
Microbiomes in Neverland
Authors: Emma Slack, Nicholas A. Bokulich
Journal: Cell Host & Microbe (2023)

Differentiating the effects of infant microbiota, developmental, and nutritional changes on immunological maturation during weaning is an ongoing challenge. In this issue of Cell Host & Microbe, Lubin and colleagues report a gnotobiotic mouse model that maintains neonatal-like microbiome composition into adulthood to help answer burning questions in this field. Differentiating the effects of infant microbiota, developmental, and nutritional changes on immunological maturation during weaning is an ongoing challenge. In this issue of Cell Host & Microbe, Lubin and colleagues report a gnotobiotic mouse model that maintains neonatal-like microbiome composition into adulthood to help answer burning questions in this field. Arresting microbiome development limits immune system maturation and resistance to infection in miceLubin et al.Cell Host & MicrobeMarch 29, 2023In BriefThe transition from a pre-weaning intestinal microbiome to an adult-like community is a critical period in host development. Lubin et al. explore the consequences of restricting the intestinal microbiome to a pre-weaning configuration on normal immune system maturation, major microbially derived metabolite generation, and susceptibility to enteric infection. Full-Text PDF
Enhancing attention in children using an integrated cognitive-physical videogame: A pilot study
Authors: J. A. Anguera, M. A. Rowe, J. J. Volponi, M. Elkurdi, B. Jurigova, A. J. Simon, R. Anguera-Singla, C. L. Gallen, A. Gazzaley, E. J. Marco
Journal: npj Digital Medicine (2023)

Inattention can negatively impact several aspects of a child's life, including at home and school. Cognitive and physical interventions are two promising non-pharmaceutical approaches used to enhance attention abilities, with combined approaches often being marketed to teachers, therapists, and parents typically without research validation. Here, we assessed the feasibility of incorporating an integrated, cognitive-physical, closed-loop video game (body-brain trainer or 'BBT') as an after-school program, and also evaluated if there were attention benefits following its use. Twenty-two children (7-12 years of age) with a range of attention abilities were recruited to participate in this proof of concept, single-arm, longitudinal study (24 sessions over 8 weeks, ~30 min/day). We interrogated attention abilities through a parent survey of their child's behaviors, in addition to objective performance-based and neural measures of attention. Here we observed 95% compliance as well as, significant improvements on the parent-based reports of inattention and on cognitive tests and neural measures of attention that were comparable in scale to previous work. Exploratory measures of other cognitive control abilities and physical fitness also showed similar improvement, with exploratory evaluation of retained benefits on the primary attention-related outcomes being present 1-year later. Lastly, there was no correlation between the baseline parent-rated inattention score and the improvement on the primary task-based measures of attention, suggesting that intervention-based benefits were not solely attained by those who stood the most to gain. These pilot findings warrant future research to replicate and extend these findings.